Adelmidrol in Chronic Sinusitis (AdeCroS)

Objectives Primary Objective To determine whether long-term treatment with adelmidrol nasal spray reduces nasal polyp size in patients with CRSwNP compared with standard treatment alone.

Secondary Objectives To evaluate changes in sinonasal symptoms. To assess changes in nasal congestion. To evaluate radiological improvement. To determine postoperative outcomes after FESS. To assess whether adelmidrol treatment may reduce the need for surgery in patients with limited disease.

To evaluate treatment safety and tolerability. Study Design Prospective Randomized Controlled Parallel-group study Single-center (or multicenter if applicable) Study Duration

Approximately 9 months per patient:

Baseline (T0) 6 months preoperative treatment (T1) Surgery (FESS) Follow-up at 1 month (T2) Follow-up at 3 months (T3) Sample Size Calculation The primary endpoint is the change in Nasal Polyp Score (NPS). Based on previous CRSwNP studies, a clinically meaningful difference between groups is expected to be approximately 1.0 point in total NPS, with an estimated standard deviation of 1.4 points.

Using:

α = 0.05 (two-sided) Power = 80% Effect size (Cohen's d) = 0.71

The required sample size is:

n= δ 2

2(Z α/2

• Z β

σ 2

Where:

Z α/2

=1.96 Z β

=0.84 σ=1.4 δ=1.0

Result:

n≈27 patients per group

Allowing for a 10-15% dropout rate:

30 patients per group

Total sample size:

60 patients (30 Control, 30 Adelmidrol). Participants Inclusion Criteria Age 18-70 years Chronic rhinosinusitis with nasal polyps according to EPOS criteria Candidate for FESS No antihistamines within 6 months No systemic or topical corticosteroids at enrollment Ability to provide informed consent Exclusion Criteria

As specified in the original protocol:

Chronic rhinosinusitis without polyps Previous sinonasal surgery within 12 months Current corticosteroid or antihistamine therapy Asthma Immunodeficiency Active purulent sinusitis requiring antibiotics Cancer treatment within previous 3 years Severe neurological disorders Anticoagulant therapy (except low-dose aspirin) Treatments Control Group

Standard therapy:

Nasal saline irrigation Intranasal corticosteroid spray Adelmidrol Group

Standard therapy plus:

Adelmidrol nasal spray Two sprays per nostril Three times daily

Treatment duration:

From enrollment until surgery Continued for 3 months after surgery Outcome Measures 1. Radiological Assessment CT Protocol Preferred imaging modality. Acquisition parameters Multidetector CT Slice thickness: 0.5-1 mm Coronal and axial reconstructions Bone and soft-tissue windows No contrast medium CT Scoring Lund-Mackay Score

Each sinus scored:

0 = no opacification

1. = partial opacification
2. = complete opacification

Sinuses assessed bilaterally:

Maxillary Anterior ethmoid Posterior ethmoid Frontal Sphenoid

Ostiomeatal complex:

0 = patent 2 = obstructed

Maximum score:

24 Higher scores indicate more severe disease. MRI Protocol MRI performed when CT is contraindicated or for detailed soft tissue evaluation.

Sequences Axial T1-weighted Axial T2-weighted Coronal T2-weighted Coronal STIR Post-contrast T1-weighted with fat suppression (if clinically indicated) Parameters Slice thickness: 3 mm Matrix: 256 × 256 Field of view: 18-22 cm

MRI evaluation includes:

Polyp extension Mucosal edema Sinus opacification Inflammatory tissue volume 2. Sinonasal Symptom Questionnaire The validated Sino-Nasal Outcome Test (SNOT-22) is recommended. Structure 22 items assessing: Nasal obstruction Rhinorrhea Postnasal drip Facial pain Smell loss Sleep quality Fatigue Emotional well-being

Each item scored:

0 = no problem

1. = very mild
2. = mild
3. = moderate
4. = severe
5. = worst possible

Total score:

0-110 Higher scores indicate worse symptoms. A reduction of ≥8.9 points is generally considered clinically meaningful. 3. Nasal Polyp Score (NPS) The NPS is assessed by nasal endoscopy. Each nasal cavity is scored separately. Scoring 0 No polyps

1 Small polyps confined to middle meatus 2 Polyps extending below middle turbinate 3 Large polyps reaching lower border of inferior turbinate 4 Large polyps causing near-complete or complete obstruction Total Score Right side + Left side

Range:

0-8 Higher scores indicate larger polyp burden. 4. Nasal Congestion Score (NCS) Patient-reported assessment of nasal blockage. Scale 0 = No congestion

1. = Mild congestion
2. = Moderate congestion
3. = Severe congestion Bilateral Score The overall score corresponds to the patient's global perception of congestion.

Range:

0-3 Higher scores indicate worse obstruction. Some studies use a daily average of morning and evening ratings; for consistency, the score recorded during study visits should be used.

Study Assessments Assessment T0 T1 T2 T3 Medical hist X Nasal endo X X X X NPS X. X X X NCS X X X X SNOT-22 X X X X CT/MRI X X X Adverse events X X X

Statistical Analysis Intention-to-treat analysis Descriptive statistics Student's t-test or Mann-Whitney U test for between-group comparisons Repeated-measures ANOVA or mixed-effects model for longitudinal outcomes Chi-square test for categorical variables Significance level: p < 0.05 Expected Results

Patients receiving adelmidrol are expected to show:

Lower Nasal Polyp Scores before surgery. Lower Nasal Congestion Scores. Better SNOT-22 scores. Improved radiological findings. Reduced postoperative recurrence. Improved healing after FESS. In selected patients with limited disease, avoidance or postponement of surgery.

These findings would support the use of adelmidrol as a mast-cell-targeted adjunctive therapy in chronic rhinosinusitis with nasal polyps.